AMSTERDAM – An early rule-out strategy based upon using two cardiac biomarkers allowed for safe discharge within a couple hours from the emergency department for most low- to intermediate-risk patients who presented with suspected acute coronary syndrome, based on the results of a randomized, multicenter trial conducted in Europe.
Moreover, the 30-day rates of major adverse cardiovascular events in the Biomarkers in Cardiology-8 (BiC-8) study were similarly low in patients discharged from the ED using the early rule-out process and in those who received standard, guideline-recommended care, which includes 6-12 hours of serial ECGs and troponin measurements in the chest pain unit, Dr. Martin Moeckel reported at the annual congress of the European Society of Cardiology.
Dr. Martin Moeckel
"This biomarker strategy using a state-of-the-art quantitative troponin assay in combination with an ultrasensitive copeptin assay has the potential to change clinical practice with high patient safety," observed Dr. Moeckel of Charité Hospital, Berlin. The copeptin test is approved for use in the European Union but remains investigational in the United States.
Based upon the results of BiC-8, this dual biomarker for early rule-out of myocardial infarction (MI) is now standard clinical practice at Charité, he added.
The rationale for developing the early rule-out strategy tested in BiC-8 lies in the serious overcrowding that is now the norm in many EDs. This overcrowding has been shown to be in and of itself a risk factor for poor outcomes. The quandary is that nearly 12% of all patients who present to the ED do so because of chest pain, yet after an extensive and time-consuming evaluation only 1 in 10 of those patients is found to actually be having an acute MI.
"Rapid rule-out of acute MI is therefore a major clinical need, saving the health care system time and resources, and saving patients unnecessary stress, anxiety, and other risks," he said.
Copeptin is a marker for vasopressin, a hemodynamic stress indicator that shoots up immediately in an acute MI. In earlier studies, a negative result for both troponin and copeptin in an initial blood sample drawn at ED presentation had a 99% negative predictive value for MI.
The BiC-8 trial included 902 low- to intermediate-risk patients who presented with suspected acute coronary syndrome (ACS) to EDs in university medical centers. All had a negative initial cardiac troponin test. They were randomized to standard care in the chest pain unit, including serial troponin testing and ECGs, or to the experimental strategy, in which physicians were informed of the copeptin results from the same initial blood sample as the troponin. If the copeptin test was positive as defined by a level of 10 pmol/L or more, the patient was hospitalized for standard care. If the copeptin result was negative, however, the patient was immediately discharged with a scheduled outpatient visit within 72 hours.
Of the patients in the copeptin group, 66% were discharged directly from the ED, compared with 12% in the standard-care group.
The 30-day incidence of major adverse cardiovascular events (MACE) was 5.5% in the standard-care group and nearly identical at 5.46% in the copeptin group. However, physicians were permitted under the study protocol to overrule negative biomarker test results on the basis of their final clinical assessment, such as if their suspicions were aroused due to recurrent symptoms or new information about the patient’s history. In this per-protocol analysis, the 30-day MACE rate was 5.68% in the standard-care group and 3.18% in the copeptin group.
MACE was defined in BiC-8 as all-cause mortality, MI, rehospitalization for ACS, acute unplanned percutaneous coronary intervention (PCI), coronary artery bypass surgery, life-threatening arrhythmia, or resuscitation from cardiac arrest.
MACE occurred in 14 copeptin-negative patients. However, 12 of the 14 were not discharged early because physicians overruled the negative biomarker results and moved the patients into standard in-hospital management. Two patients, or 0.6% of those discharged from the ED on the basis of a negative copeptin test had adverse events: One was rehospitalized on day 23 and underwent acute unplanned PCI on the next day, and the other was rehospitalized on day 4 and underwent coronary artery bypass graft surgery on day 12.
Dr. Donna K. Arnett
American Heart Association Immediate Past President Donna K. Arnett, Ph.D., said in an interview that she’d really like to see a second, confirmatory randomized trial before this early rule-out strategy is widely adopted. She considers the lost-to-follow-up rate uncomfortably high: 63 patients in the intention-to-treat analysis, and another 75 not accounted for in the per-protocol analysis, noted Dr. Arnett, professor and chair of the epidemiology department at the University of Alabama, Birmingham.